营养过剩和线粒体蛋白质组及功能改变导致糖尿病中的神经退行性病变。
Nutrient excess and altered mitochondrial proteome and function contribute to neurodegeneration in diabetes.
机构信息
Division of Neurodegenerative Disorders, St Boniface Hospital Research Centre, Winnipeg, MB, Canada R2H 2A6.
出版信息
Mitochondrion. 2011 Nov;11(6):845-54. doi: 10.1016/j.mito.2011.06.007. Epub 2011 Jul 2.
Abstract
Diabetic neuropathy is a major complication of diabetes that results in the progressive deterioration of the sensory nervous system. Mitochondrial dysfunction has been proposed to play an important role in the pathogenesis of the neurodegeneration observed in diabetic neuropathy. Our recent work has shown that mitochondrial dysfunction occurs in dorsal root ganglia (DRG) sensory neurons in streptozotocin (STZ) induced diabetic rodents. In neurons, the nutrient excess associated with prolonged diabetes may trigger a switching off of AMP kinase (AMPK) and/or silent information regulator T1 (SIRT1) signaling leading to impaired peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1α) expression/activity and diminished mitochondrial activity. This review briefly summarizes the alterations of mitochondrial function and proteome in sensory neurons of STZ-diabetic rodents. We also discuss the possible involvement of AMPK/SIRT/PGC-1α pathway in other diabetic models and different tissues affected by diabetes.
摘要
糖尿病性神经病是糖尿病的一种主要并发症，会导致感觉神经系统的进行性恶化。线粒体功能障碍被认为在糖尿病性神经病中观察到的神经退行性变的发病机制中起重要作用。我们最近的工作表明，线粒体功能障碍发生在链脲佐菌素（STZ）诱导的糖尿病啮齿动物的背根神经节（DRG）感觉神经元中。在神经元中，与长期糖尿病相关的营养过剩可能会触发 AMP 激酶（AMPK）和/或沉默信息调节因子 T1（SIRT1）信号的关闭，导致过氧化物酶体增殖物激活受体 γ 共激活因子-1（PGC-1α）表达/活性受损和线粒体活性降低。本文简要总结了 STZ 糖尿病啮齿动物感觉神经元中线粒体功能和蛋白质组的改变。我们还讨论了 AMPK/SIRT/PGC-1α 通路在其他糖尿病模型和受糖尿病影响的不同组织中的可能参与。
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本文引用的文献
1
Sensory neuropathy attributable to loss of Bcl-w.归因于 Bcl-w 缺失的感觉神经病变。
J Neurosci. 2011 Feb 2;31(5):1624-34. doi: 10.1523/JNEUROSCI.3347-10.2011.
2
Protective effect of N-acetylcysteine supplementation on mitochondrial oxidative stress and mitochondrial enzymes in cerebral cortex of streptozotocin-treated diabetic rats.N-乙酰半胱氨酸对链脲佐菌素诱导糖尿病大鼠大脑皮质线粒体氧化应激和线粒体酶的保护作用。
Mitochondrion. 2011 Jan;11(1):214-22. doi: 10.1016/j.mito.2010.09.014. Epub 2010 Nov 7.
3
Diminished superoxide generation is associated with respiratory chain dysfunction and changes in the mitochondrial proteome of sensory neurons from diabetic rats.超氧化物生成减少与呼吸链功能障碍以及糖尿病大鼠感觉神经元线粒体蛋白质组的变化有关。
Diabetes. 2011 Jan;60(1):288-97. doi: 10.2337/db10-0818. Epub 2010 Sep 28.
4
Protein deacetylation by sirtuins: delineating a post-translational regulatory program responsive to nutrient and redox stressors.Sirtuins 通过蛋白去乙酰化作用：描绘出响应营养和氧化还原应激的一种翻译后调控程序。
Cell Mol Life Sci. 2010 Sep;67(18):3073-87. doi: 10.1007/s00018-010-0402-y. Epub 2010 Aug 3.
5
AMP-activated protein kinase and its downstream transcriptional pathways.AMP 激活的蛋白激酶及其下游转录途径。
Cell Mol Life Sci. 2010 Oct;67(20):3407-23. doi: 10.1007/s00018-010-0454-z. Epub 2010 Jul 17.
6
Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1.脂联素和脂联素受体 1 通过 Ca(2+) 和 AMPK/SIRT1 调节 PGC-1α 和线粒体。
Nature. 2010 Apr 29;464(7293):1313-9. doi: 10.1038/nature08991. Epub 2010 Mar 31.
7
Mitochondrial respiratory chain dysfunction in dorsal root ganglia of streptozotocin-induced diabetic rats and its correction by insulin treatment.链脲佐菌素诱导糖尿病大鼠背根神经节中线粒体呼吸链功能障碍及胰岛素治疗的纠正。
Diabetes. 2010 Apr;59(4):1082-91. doi: 10.2337/db09-1299. Epub 2010 Jan 26.
8
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10
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